This application is directed to the career development of Dr. Rachel Saunders-Pullman as a clinical researcher in the study of hormonal effects on Parkinson's Disease and other neurodegenerative disorders. During the period of this grant she will focus on gender differences and the role of hormones in the development of Parkinson's disease (PD). As hormone physiology is complex, and estrogenic compounds can be carcinogenic as well as beneficial, the assessment of the role of estrogen and gender differences and the planning of clinical trials requires multi-disciplinary knowledge and training. The candidate has constructed a training program with areas of emphasis in epidemiology, neuroscience and neuroendocrinology, cognition and movement disorders using an integrated plan of research, coursework, lectures, and rounds. Her primary sponsor, Dr. Richard Lipton will oversee the methods and the candidate's development in epidemiology and cognition as well as the overall training. The co-sponsor, Dr. Susan Bressman will provide guidance in the field of movement disorders. A consultant team of Dr. Anne Etgen, Dr. Nanette Santoro and Dr. Charles Hall will complement with expertise in neuroscience and neuroendocrinology and biostatistics, respectively. In order to address gender related differences in risk of PD and clinical features of PD, and whether hormonal factors account for these differences, three separate studies with differing study designs are proposed. These studies were designed to provide complementary answers to specific research questions and to give the candidate hands-on, mentored exposure to three major types of epidemiologic research 1) a clinic-based prospective study of gender differences in the natural history and disease course in early PD, 2) a case-control study of pharmacy records to assess whether exogenous estrogen decreases the risk of PD and 3) a cross-sectional and a prospective evaluation of the role of gender and endogenous hormone levels on motor control measures in aging and pre-clinical parkinsonism in an established cohort study. Through the aggregate of the training program and supervised research, the candidate will emerge as an independent researcher well prepared to answer questions of the role of hormones in neurodegenerative diseases and movement disorders. [unreadable] [unreadable]